1. Field of the Invention
This invention relates generally to the field of inducing the nucleation of selected crystal polymorphs from supersaturated solutions and specifically to a process of inducing the nucleation of selected crystal polymorphs from supersaturated solutions by using laser light to induce nucleation, and switching the polarization of the laser light to select a particular crystal polymorph. This invention further relates to the ability to change the crystal polymorph induced by laser nucleation by switching the polarization from linear to circular to elliptical, thus allowing the selection of a particular polymorph, whether stable or metastable.
2. Prior Art
The crystal structure of a material determined by x-ray diffraction gives a complete picture of the arrangement of the atoms (or molecules) of the chemical species in the crystalline state. It is possible, however, for a given chemical species to have the ability to crystallize into more than one internally distinct structure. This ability is called polymorphism (or allotropism if the species is an element). Different polymorphs of the same material can display significant changes in their properties as well as in their structure.
The term polymorphism is contrasted with morphology. Crystals are solids with the atoms, molecules, or ions in a regular repeating structure. The overall external form is referred to as crystal morphology. The term morphology refers to the external shape of the crystal and the planes present, without reference to the internal structure. Crystals obtained experimentally can display different morphology based on different conditions, such as, for example, growth rate, stirring, and the presence of impurities. In contrast, as stated above, polymorphism refers to the internal alignment and orientation of the molecules. A substance can have several distinct polymorphs and only one morphology, or can have several distinct morphologies for only one polymorph. A change in morphology does not imply that a new polymorph arises, and vice versa. Unlike with different morphologies, one cannot tell by visual inspection whether one has a different polymorph.
The prior art is directed to nucleating substances to achieve a desired morphology and crystal structure that is known to arise under the given set of conditions. There is no discussion in the prior art of using specifically polarized light to achieve crystallization or a specific crystal polymorph. Further, there is no discussion in the prior art of nucleating a new or unknown crystal structure (a new polymorph) or of an unexpected structure (a known polymorph that would not normally occur under these conditions). It is important to note that crystals of a given substance with different morphologies (external shape) have the same physical properties (such as melting point, solubility, electrical conductivity, etc) while different polymorphs (internal structure) of the same substance have different properties (e.g., diamond and graphite, which are different polymorphs of carbon).
Polymorphism is quite common in the elements and in inorganic and organic compounds and results in property changes. A dramatic example is carbon, which can crystallize as graphite or as diamond. Diamond is a cubic crystal, whereas graphite is a hexagonal crystal. In addition, properties such as hardness, density, shape, vapor pressure, dissolution rate, and electrical conductivity are all quite different for these two solids. These major differences in the properties of two polymorphs are not unique to carbon and can occur in all materials that display polymorphism. Many of the early identifications of polymorphs were minerals, such as calcium carbonate, which has three polymorphs (calcite, aragonite, and vaterite) and zinc sulfide, which has three polymorphs (wurtzite, sphalerite, and matraite). Some well known species have large numbers of polymorphs, for example water, which has eight different solid forms of ice. Organic molecular crystals often have multiple polymorphs that can be of great significance in the pharmaceutical, dye and explosives industries.
Under a given set of conditions, one polymorph is the thermodynamically stable form. This does not mean that other polymorphs cannot exist or form at these conditions, only that one polymorph is stable and other polymorphs present within the solution can transform to the stable form. An example of this can be seen in heating (or cooling) a crystalline material with multiple polymorphs. As the temperature changes, the material can eventually enter a region where another polymorph is the stable form. The transformation of one polymorph to another, however, will occur at some rate that may be rapid or very slow. The transformation rate varies because the rate of transition of polymorphs depends on the type of structural changes that are involved.
Transformations can be categorized by the types of structural changes involved, which can roughly be related to the rate of transformation. For example, a transformation in which the lattice network is bent but not broken can be rapid. This type of transformation is known as displacive transformation of secondary coordination. Another type of rapid transformation can involve the breakage of weaker bonds in the crystal structure with the stronger bonds remaining in place. This is then followed by the rotation of parts of the molecule about the structure and the formation of new bonds. This type of transformation is a rotational disorder transformation. Slow transformations usually involve the breakage of the lattice network and major changes in the structure or type of bonding.
Polymorphic transformations also can be classified as first-or second-order transitions. In a first-order transition, the free energies of the two forms become equal at a definite transition temperature, and the physical properties of the crystal undergo significant changes upon transition. In a second-order transition, there is a relatively small change in the crystal lattice, and the two polymorphic forms will be similar. There is no abrupt transition point in a second order transition, although the heat capacity rises to a maximum at a second order transition point.
When a material is crystallized from solution, the transition between polymorphs can occur at a much higher rate because the transition is mediated by the solution phase. Polymorphs of a given material will have different solubilities at a given temperature, with the more stable polymorph having a lower solubility (and a higher melting point) than the less stable polymorph. If two polymorphs are in a saturated solution, the less stable polymorph will dissolve and the more stable polymorph will grow until the transition is complete. The rate of the transition is a function of the difference in the solubility of the two forms and the overall degree of solubility of the compounds in solution. This transition requires that some amount of the stable polymorph be present, meaning that the stable polymorph must nucleate at least one crystal for the transition to begin. If a slurry of solution and crystals of a polymorph stable at a high temperature is cooled to a lower temperature, where another polymorph is the stable phase, the transition of the crystals already present will depend on the presence of nuclei of the new stable phase. The more of these nuclei present, the faster the transition will occur.
Another interesting feature of organic molecular crystals is that the molecular conformation (the shape of the molecule) of a species can be different in two polymorphs of the same material. The same molecule can display different shapes (conformations by rotations about single bonds for example). Conformational polymorphism is the existence of polymorphs of the same substance in which the molecules present are in different conformations.
It is known that by subjecting some supersaturated solutions to laser light, the onset of nucleation occurs. Prior to nucleation, the supersaturated solution contains clusters of molecules that are not arranged in the lattice structure of a crystal. The laser light helps to align or organize the molecules in the clusters into a lattice arrangement resulting in the formation of nuclei and, after time, crystals. For a urea solution, it was shown that the laser could induce nucleation and the one and only known and expected polymorph for urea was obtained. Garetz, B. A. et al., Nonphotochemical, Polarization-Dependent, Laser-Induced Nucleation in Supersaturated Aqueous Urea Solutions, Physical Review Letters, Vol. 77, No. 16, pp. 3475-6 (1996).
In the Garetz article, it was shown that pulses from a Q-switched Nd:YAG laser could induce nucleation in supersaturated solutions. In the case of urea, the crystallites that are formed have the same structure as crystallites that form when the same solution spontaneously nucleates. After supersaturated solutions with concentrations in the range of 11.5-13.5M were aged for one to two weeks, the solutions were illuminated with the 1.06-xcexcm wavelength, plane-polarized output of a Quanta-ray DCR-1 Q-switched Nd:YAG laser. A portion of the doughnut-shaped beam with approximately constant intensity was selected by passing the beam through an aperture with an area of xcx9c2 mm2. With the laser oscillator alone, the measured energy per pulse was 0.02 J, while with the amplifier added, it was 0.1 J. The measured pulse width was 20 ns, and the pulse repetition rate was 10 pps. The unamplified and amplified pulses thus had intensities of 50 and 250 MW/cm2, respectively. Exposure of the aged solutions to laser pulses from the oscillator alone was not sufficient to induce nucleation. With the amplifier added, nucleation typically occurred within 10-20 s.
The urea solutions reported in Garetz are highly transparent at the laser wavelength of 1.06 xcexcm, so that photochemical effects are improbable. Therefore, the most likely candidates for laser-solution interactions are electric-field effects, such as the optical Kerr effect or electrostriction. The applied electric field apparently aids in organizing existing pre-nucleating clusters, increasing the chances that one will nucleate and grow.
The Garetz article does not disclose switching the polarization of the light either to cause the nucleation of a desired specific polymorph or to cause the creation of an unexpected (new) polymorphs, as disclosed and claimed in the present patent application. Importantly, as stated, urea has only one polymorph, which will be the polymorph in solution in the advent of nucleation. Therefore, it does not matter in the Garetz article process which polarization state is usedxe2x80x94both should result in the single known urea polymorph. More specifically, the Garetz article discloses the effect laser-induced nucleation has on the orientation of the molecules and that the polarization dependence of the crystallite orientation is consistent with a mechanism in which the electric field of the light plays a major role and that urea molecules are being aligned by the applied optical field, just as they are in the optical Kerr effect, also known as light-induced birefringence. The Garetz article further discloses that only urea""s anisotropic polarizability is responsible for electric-field-induced alignment at optical frequencies, thus, according to the Garetz mechanism, urea molecules in a cluster will tend to align with their C2 rotation axes parallel to an applied electric field, E, growing into a crystallite with the needle axis parallel to E.
The discovery published in the Garetz article is a photophysical phenomenon in which the laser induced crystallization of urea causes the alignment of the urea molecules by the applied optical field. The crystals that result from the experimentation disclosed in the Garetz article were known and expected crystals. The novelty of the Garetz article is that the laser light causes the urea molecules to align, facilitating the nucleation into the known crystals. This is substantially different from the present invention, which is the creation of unexpected and/or new polymorphs not normally obtained using current art nucleation methods by switching the polarization of the incident light. Most importantly, the Garetz article does not disclose a relation between the polarization of light source and polymorphs.
U.S. Pat. No. 5,976,325 to Blanks discloses a method for producing a substance with a known morphology and crystal structure in aluminate solution. Blanks xe2x80x2325 discloses a self-seeding process to obtain the most stable crystal structure of sodium aluminate from a supersaturated aluminate solution (i.e. Bayer Process solution) and does not implicate the polymorphism of the substance. More distinctively, the process in Blanks xe2x80x2325 is primarily for destroying impurities in the solution, and the light used is absorbed by the materials.
Blanks xe2x80x2325 discloses a process for forming a precipitated alumina hydrate, comprising the steps of providing a sodium aluminate solution; and illuminating said sodium aluminate solution with light wave energy produced by the near infrared wavelength, linearly polarized output of a laser to form a precipitated alumina hydrate where no external seed is added. Much like the Garetz article, Blanks xe2x80x2325 discloses a method for obtaining a known crystal in a process for forming a precipitated alumina hydrate such as aluminum trihydroxide by providing a supersaturated sodium aluminate solution and treating the solution by illumination with pulsed near infrared light wave energy, spatially and temporally overlapped inside the solution, so as to produce a photo-induced nucleation of purified gibbsite crystals, without the need for external seed.
Blanks ""325 does not disclose or claim, or even discuss, the formation of different or unexpected polymorphs through the switching of the polarization state of the incident light. Blanks ""325 does not disclose whether a specific polymorph of alumina hydrate is desired and, more importantly, whether a different polymorph of alumina hydrate that is not typically created for use in the purification process (or an unknown polymorph of alumina hydrate) is created or can be created by switching the polarization state of the light.
Blanks ""325 discloses a laser treatment process for introducing infrared light into green Bayer liquor to provide enhancements in alumina yield of as much as 50 grams/liter without the addition of seed. This, coupled with the lack of disclosure on how to prepare different or unknown polymorphs, and polymorphs that normally would not result under the same conditions without the use of the selected light, or to switch the polarization state of the light to obtain a different polymorph, indicates that Blanks ""325 does not contemplate the present invention.
The mechanism by which the Blanks ""325 method works also is different than that of the present patent application. Blanks ""325 discloses that the laser removes undesirable organic compounds that are generally considered as inhibitors to alumina hydrate precipitation. In other words, the laser works by photochemically destroying organic impurities, thus permanently changing the conditions (i.e., with inhibitors removed) under which the nucleation proceeds. The method therefore requires that the laser light be absorbed by organic impurities in the solution, so that in Blanks ""325 the wavelength of the laser needs to be tuned to match the absorption bands of the organic impurities in their samples. One feature of Blanks ""325 is that by absorbing near infrared light, they are able to induce the photochemistry needed to destroy their organic impurities. In contrast, the present invention involves essentially no light absorption by the sample.
Therefore, it can be seen that there exists a need for a process for selectively nucleating and creating known polymorphs of known substances and for nucleating and creating new polymorphs of known substances for use in laboratory and industrial settings. It is to this need that the present invention is directed.
Crystallization from solution occurs from a supersaturated solution. Supersaturated solutions are metastable, meaning that they sometimes will not spontaneously crystallize. This is particularly true for organic molecular crystals because of the difficulty the molecules have in finding the correct lattice positions needed to form a solid crystalline material.
Briefly, the present invention is a novel method for creating new or unexpected polymorphs of known substances by means of irradiating a solution with a selected polarization of light. It has been found that switching the polarization of the light used in laser-induced non-photochemical nucleation can result in the creation of different polymorphs. For example, using light having linear polarization can result in the nucleation of a first polymorph, using light having circular polarization can result in the nucleation of a second polymorph, and using light having elliptical polarization may result in the nucleation of a third polymorph. Further, the method is repeatable, with a specific polymorph arising from the use of one polarization state, a different specific polymorph arising from the use of a second polarization state, and possibly a different specific polymorph arising from the use of a third polarization state.
Further, this invention has the potential for creating new polymorphs having internal crystal structures that are different than those of currently known polymorphs (new polymorphs) or different than what would be expected by one of ordinary skill in the art without use of the present method (unexpected polymorphs). Surprisingly, the new or unexpected polymorphs can be created without essentially chemically affecting or influencing the solution (that is, changing the chemistry of the solution).
In effect, the present method is a non-chemical method of affecting the solution. This can be important in both the laboratory and in industry. Because different polymorphs have different solid properties, different polymorphs behave differently when used for applications. For examples, a different polymorph of a dye would give a different color, and different polymorphs of drugs can have different bioavailability and dissolution properties. Much effort is spent in trying to find if a particular substance has additional polymorphs and in trying to prepare a particular polymorph. Developing and producing new polymorphs provides significant advantages both to research facilities and to commercial manufacturers, as both constantly are attempting to develop new products having better properties through the use of polymorphs.
This invention makes use of high-intensity pulses of laser light to induce nucleation in a supersaturated solution of a known substance. By subjecting the supersaturated solutions to laser light, the onset of nucleation occurs. By switching the polarization state of the light, different polymorphs can be created. That is, using one polarization state of the laser light can produce one polymorph, while using a different polarization state of the laser light can produce a different polymorph. Depending on the system, macroscopic crystals form on, for example, a timescale of seconds (aqueous urea) to hours (aqueous glycine).
Although various different types of lasers are suitable for this process, the preferred laser light is at near-infrared wavelengths, where many solutions are transparent, minimizing the absorption between laser and solution. More likely interactions involve responses of molecules to the electric field associated with the laser light, such as the optical Kerr effect (the field-induced alignment of molecules) or electrostriction (the field-induced movement of molecules into regions of high electric field). In each of these interactions, the electric field of the light polarizes a molecule, meaning that it applies forces to the electrons and nuclei that comprise the molecule, and induces transient changes in the charge distribution in the molecule. Whatever the interactions between light and molecule, they aid in the formation of an ordered cluster of molecules that goes on to grow into a crystal.
The present invention also can be used to cause the nucleation and crystal growth to occur in such a way as to obtain a crystal polymorphism that is unexpected under given conditions by the person of ordinary skill in the art. Previously, under a defined set of conditions, specific polymorphs will be present in the solution and will be known and expected by the person of ordinary skill in the art and a variation in the defined conditions can change the expected and known polymorph. However, the present method can be used to prepare new polymorphs of material that would not ordinary be observed to occur or prepare polymorphs that are not expected by the person of ordinary skill in the art to occur under given conditions in the absence of the method, simply by switching the polarization state of the light.
One feature of this invention generally is the use of laser light to induce the nucleation of a polymorph from a supersaturated solution that is different from the polymorph that would spontaneously nucleate from the supersaturated solution under the same general conditions, but in the absence of the selected polarization of the laser light.
Another feature of this invention is the use of continuous wave or pulsed lasers, in various polarization states (e.g., plane polarization versus circular polarization versus elliptical polarization), at various wavelengths where the supersaturated solution does not absorb, at various laser powers, pulse lengths, pulse repetition rates and exposure times, to induce the nucleation of a polymorph from a supersaturated solution that is different from the polymorph that would spontaneously nucleate from the supersaturated solution under the same general conditions, but in the absence of the selected polarization of the laser light.
Another feature of this invention is the use of various different process conditions (i.e., at various temperatures depending on the solubility of the compound being subjected to the light, various aging times, various supersaturation levels; various methods of achieving supersaturation such as cooling, heating, solvent evaporation, and changing solvent composition; and various different solvents such as organic or inorganic solvents) to induce the nucleation of a polymorph from a supersaturated solution that is different from the polymorph that would spontaneously nucleate from the supersaturated solution under the same general conditions, but in the absence of the selected laser light.
Another feature of this invention is to provide a method for inducing an unknown and/or unexpected polymorph and spontaneous nucleation in a solution under a set of conditions through the use of a laser light without essentially changing the chemistry of the solution.
These features, and other features and advantages of the present invention will become more apparent to those of ordinary skill in the art when the following detailed description of the preferred embodiments is read in conjunction with the attached figures.